VK-2019 for Nasopharyngeal Cancer

Overseen by A. Dimitrios Colevas

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Stanford University

Must not be taking: Anticancer therapies

Disqualifiers: Cardiopulmonary diseases, CNS involvement, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing VK 2019, a new cancer treatment, on patients with a specific type of throat cancer linked to the Epstein-Barr virus who have no other treatment options. The goal is to see if VK 2019 can effectively fight the cancer and to understand its safety and effects on patients.

Will I have to stop taking my current medications?

The trial requires that you do not take any other systemic cancer treatments, including complementary or alternative therapies, while participating. It does not specify about other medications, so you should discuss your current medications with the trial team.

What data supports the effectiveness of the drug VK-2019 for treating nasopharyngeal cancer?

Research shows that VK-2019 is a specific inhibitor of EBNA1, a protein critical for the maintenance of the Epstein-Barr virus in cancer cells. Similar EBNA1 inhibitors have shown strong anti-cancer effects in models of other Epstein-Barr virus-associated cancers, suggesting potential effectiveness for nasopharyngeal cancer. ^{1 2 3 4 5}

What safety data exists for VK-2019 in humans?

VK-2019 is currently in phase 1 development, which means it is being tested for safety in humans, but specific safety data from these trials is not provided in the available research articles. ^{1 2 4 6 7}

How does the drug VK-2019 work differently from other treatments for nasopharyngeal cancer?

VK-2019 is unique because it specifically targets and inhibits EBNA1, a protein crucial for the Epstein-Barr virus (EBV) that is associated with nasopharyngeal cancer. This targeted approach is different from other treatments that may not specifically address the EBV component of the cancer. ^{1 2 6 7 8}

Research Team

A. Dimitrios Colevas

Principal Investigator

Stanford Universiy

Eligibility Criteria

Adults with EBV-positive nasopharyngeal cancer not eligible for standard treatments can join. They must have good kidney function, controlled protein in urine, agree to birth control use, and be generally well enough (ECOG ≤2). Prior treatments should be completed with recovered side effects (except stable chronic issues), and blood counts need to meet specific levels.

Inclusion Criteria

Platelet count > 75 x 103/ µL (transfusion to achieve this level is NOT permitted)

My white blood cell count is healthy without medication.

My urine protein levels are low, under 1g/24 hours if tested with a 24-hour collection.

Exclusion Criteria

Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the subject inappropriate for entry into the study

I am not pregnant, confirmed by a test.

I am HIV positive but have a stable condition with effective treatment, no opportunistic infections, a CD4 count above 250, and an undetectable viral load.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VK 2019 in cycles of 28 days, up to 12 cycles, until progression or dose limiting toxicity

12 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Extension

Participants may continue to be monitored for overall survival and progression-free survival

24 months

Treatment Details

Interventions

• VK-2019 (Small Molecule)

Trial Overview The trial is testing VK-2019's effectiveness against EBV-related nasopharyngeal carcinoma when no other treatment options are available. It includes pharmacokinetic and pharmacodynamic studies to understand how the drug behaves in the body and its biological effects.

Participant Groups

Group I: VK-2019_arm Experimental Treatment 1 Intervention

Dose escalation and expansion up to 31 additional patients at a maximum of 1800 mg twice daily. Cycles will be defined as 28 days of treatment, subjects will receive VK 2019 until progression or dose limiting toxicity, for up to 12 cycles.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Silencing the Epstein-Barr virus nuclear antigen 1 (EBNA1) in nasopharyngeal carcinoma (NPC) cells significantly inhibited their growth and induced a G1-phase cell cycle arrest, suggesting a potential therapeutic target for NPC.

The study demonstrated that down-regulation of EBNA1 led to decreased levels of key cell cycle regulators (c-myc, CDK4, CDK6, and pRb), which are crucial for cell proliferation, indicating a mechanism by which EBNA1 promotes cancer cell growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of Epstein-Barr virus nuclear antigen 1 on cell proliferation and cell cycle in nasopharyngeal carcinoma cells]. Wan, RQ., Li, XP., Wang, L., et al.[2019]

VK-2019 is a specific inhibitor of the EBNA1 protein from the Epstein Barr virus, which is crucial for the replication of EBV in cancer cells, and is currently being tested in phase 1 trials for treating EBV-associated cancers.

A reliable method for measuring VK-2019 levels in human plasma was developed, showing that the drug is stable for up to 18 months at -70°C, which is important for understanding its pharmacokinetics in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of VK-2019, a selective EBNA1 inhibitor. Davis, MT., Anders, NM., Colevas, AD., et al.[2023]

The meta-analysis of 21 studies involving 2986 nasopharyngeal carcinoma (NPC) patients and 3507 controls found that serum VCA-IgA has a high diagnostic accuracy for NPC, with a sensitivity of 83% and specificity of 88%.

Combining multiple EBV antigens for testing significantly improved diagnostic performance, achieving a sensitivity of 93% and specificity of 95%, suggesting that using a panel of tests may be more effective than relying solely on the VCA-IgA assay.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Value of Serum Epstein-Barr Virus Capsid Antigen-IgA for Nasopharyngeal Carcinoma: a Meta-Analysis Based on 21 Studies. Chen, Y., Xin, X., Cui, Z., et al.[2019]

The small molecule inhibitor VK-1727 effectively inhibits cell growth and proliferation in EBV-positive gastric carcinoma (EBVaGC) models, demonstrating selective action against these cancer cells.

In animal studies, VK-1727 significantly reduced tumor growth in EBVaGC xenografts, suggesting that targeting the Epstein-Barr virus nuclear antigen 1 (EBNA1) could be a promising treatment strategy for patients with this type of gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EBNA1 inhibitors have potent and selective antitumor activity in xenograft models of Epstein-Barr virus-associated gastric cancer. Soldan, SS., Anderson, EM., Frase, DM., et al.[2022]

EBNA1 protein is highly expressed in nasopharyngeal carcinoma (NPC) tissues and is linked to lymph node metastasis, suggesting its potential role as a biomarker for cancer progression.

Overexpression of EBNA1 in NPC cell lines promotes epithelial-mesenchymal transition (EMT) by inhibiting microRNA 200a and 200b, leading to increased levels of ZEB1 and ZEB2, which are key regulators of EMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epstein-Barr virus nuclear antigen 1 (EBNA1) protein induction of epithelial-mesenchymal transition in nasopharyngeal carcinoma cells. Wang, L., Tian, WD., Xu, X., et al.[2019]

The study identified the V-val subtype of the Epstein-Barr virus nuclear antigen (EBNA)-1 as the dominant variant in Chinese populations, particularly in cases of nasopharyngeal carcinoma (NPC) and Hodgkin's disease, suggesting its significant role in these malignancies.

In contrast, the V-val subtype was not found in Danish samples, indicating that it is not restricted to the oral compartment and may be more prevalent in Asian populations, highlighting geographical differences in EBV-associated tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EBNA-1 sequence variation in Danish and Chinese EBV-associated tumours: evidence for geographical polymorphism but not for tumour-specific subtype restriction. Sandvej, K., Zhou, XG., Hamilton-Dutoit, S.[2022]

The study found that the EBV-encoded protein EBNA 1, when expressed in an EBV-negative nasopharyngeal carcinoma (NPC) cell line, led to less differentiated cell growth and increased tumorigenicity and metastasis in mice.

These findings suggest that EBNA 1 may significantly contribute to the aggressive progression of NPC, highlighting its potential role in the disease's development and progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced malignant progression of nasopharyngeal carcinoma cells mediated by the expression of Epstein-Barr nuclear antigen 1 in vivo. Sheu, LF., Chen, A., Meng, CL., et al.[2006]

The study identified a new subvariant of the EBV EBNA1 gene, specifically P-Thr-sv-5, which shows significant clustering in nasopharyngeal carcinoma (NPC) cases, suggesting its potential as a viral biomarker for this type of cancer.

Statistical analysis of 40 NPC biopsies, 31 mononucleosis plasma samples, and 16 renal transplant plasma samples revealed distinct differences in EBNA1 subvariant distribution, indicating that certain EBNA1 polymorphisms may be associated with the development of malignancies like NPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The sequence analysis of Epstein-Barr virus EBNA1 gene: could viral screening markers for nasopharyngeal carcinoma be identified? Banko, AV., Lazarevic, IB., Karalic, DZ., et al.[2020]

References

1. China pubmed.ncbi.nlm.nih.gov

[Effect of Epstein-Barr virus nuclear antigen 1 on cell proliferation and cell cycle in nasopharyngeal carcinoma cells]. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of VK-2019, a selective EBNA1 inhibitor. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Diagnostic Value of Serum Epstein-Barr Virus Capsid Antigen-IgA for Nasopharyngeal Carcinoma: a Meta-Analysis Based on 21 Studies. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

EBNA1 inhibitors have potent and selective antitumor activity in xenograft models of Epstein-Barr virus-associated gastric cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Epstein-Barr virus nuclear antigen 1 (EBNA1) protein induction of epithelial-mesenchymal transition in nasopharyngeal carcinoma cells. [2019]

6. England pubmed.ncbi.nlm.nih.gov

EBNA-1 sequence variation in Danish and Chinese EBV-associated tumours: evidence for geographical polymorphism but not for tumour-specific subtype restriction. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Enhanced malignant progression of nasopharyngeal carcinoma cells mediated by the expression of Epstein-Barr nuclear antigen 1 in vivo. [2006]

8. Germany pubmed.ncbi.nlm.nih.gov

The sequence analysis of Epstein-Barr virus EBNA1 gene: could viral screening markers for nasopharyngeal carcinoma be identified? [2020]